A novel finding from the NICHD trial was that serum levels of active, hormonal vitamin D (1,25(OH)2D) during pregnancy were optimized at twice the level normally observed in non-pregnant women, levels that would be considered toxic in nonpregnant individuals. At no other time in life does this relationship exist. Is the hormone at such levels driving some vital process during pregnancy? If so, what is that process? There are hints as to why 1,25(OH)2D is elevated in pregnant women. During pregnancy, the maternal immune system undergoes drastic changes for fetal protection. For example, if a solid organ composed of 50% mismatched cell markers (antigens) was transplanted into a new host, it would be rejected within hours; however, a fetus that is 50% mismatched with paternal antigens is protected from immune destruction through a process known as immune privilege. During pregnancy the body increases immune suppressive cells, reduces highly activated natural killer and cytotoxic T-cells with capacity to destroy the fetus and still has the capacity to fight off foreign pathogens. While the mechanisms that orchestrate this complex balance are unknown, we hypothesize that due to vitamin D's ability to regulate immune cells, vitamin D is responsible for many immune alterations associated with fetal immune privilege. We further hypothesize that correction of vitamin D deficiency during pregnancy will protect against immune-mediated disorders such as recurrent miscarriage, preterm birth, bacterial infections, periodontal inflammation and gestational diabetes. This premise, tested and confirmed by this project, will lead to public policy changes and equality in vitamin D status during pregnancy. To test the validity of these hypotheses, the goals of this project are as follows: